The overall objective of this research proposal is to evaluate the hypothesis that therapeutic ultrasound (TUS) impacts the healing process by modulating macrophage activity. The specific aims of this project are to: 1) Evaluate cytokine expression and deposition in a cell culture model using macrophages exposed to calibrated doses of TUS at frequencies of 1MHz and 3MHz and 2) Evaluate altered cytokine gene expression in macrophages following exposure to calibrated TUS doses at frequencies of 1MHz and 3MHz. To address these specific aims, I will utilize cultured macrophages treated with TUS in vitro and then assay the conditioned media for various markers of response, i.e. cytokine release into the media, and fibroblast proliferation and neutrophil apoptosis induced by the conditioned media. Also, I will investigate changes in cytokine gene expression following exposure to calibrated TUS doses. Gene expression data will be compared with cytokine release data in an effort to delineate whether different TUS treatment frequencies and doses affect release of preformed substances or induce gene upregulation and subsequent protein release. [unreadable] [unreadable]